ELSEVIER Journal of Chromatography B, 680 (1996) 243-253 JOURNAL OF CHROMATOGRAPHY B: BIOMEDICAL APPLICATIONS Release of 5-fluorouracil from poly(acrylamide-co-monopropyl itaconate) hydrogels a ..- a* M. Dolores Blanco , Olga Garcfa a, Rosa Olmo a, Jos6 M. Teljon ' , Issa Katime b "Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad Computense de Madrid, E-28040 Madrid, Spain "Grupo de Nuevos Materiales, Departamento de Quimica Fisica Facultad de Ciencias, Universidad del Pals Vasco, Apartado 644, Bilbao, Spain Abstract The aim of this work was to test the application of copolymeric poly(acrylamide-co-monopropyl itaconate) (A-MPI) hydrogels on the release of 5-fluorouracil (5-FU). The equilibrium degree of swelling in saline solution was 83 - 2%. 5-FU, as the sodium salt, was trapped in gels by placing it in the polymerization feed mixture. The diffusion coefficients for both swelling of the gels and the release of 5-FU were determined, in addition to the activation energies for both processes. To determine the applicability of these copolymers, A-MPI (75:25) gel was subcutaneously implanted in rats and the drug plasma concentration was determined by HPLC. Keywords: Hydrogels; 5-Fluorouracil; Poly(acrylamide-co-monopropyl itaconate) 1. Introduction Classically, anticancer drugs are administered intravenously and their distribution throughout the body is a function of physico-chemical prop- erties of the molecule. A pharmacologically active concentration is reached in the tumour tissue at the expense of massive side-effects in the rest of the body. For cytostatic compounds, this poor specificity raises a toxicological prob- lem that presents a serious obstacle to effective therapy. Efforts made to develop more rational approaches to specific cancer therapy have re- sulted in the concept of controlled-release sys- * Corresponding author. 0378-4347/96/$15.00 © 1996 Elsevier Science B.V. All rights SSDI 0378-4347(95)00401-7 tems from different matrices. The main polymers used for both biomedical applications and con- trolled-release systems of many drugs are hydro- gels [1,2]. Hydrogels are characterized by their capacity to absorb water and other solvents. The absorp- tion of a solute into the network and the con- trolled release of the solute into an aqueous environment are both closely related to the swelling properties of the network involved [3]. The utility of the hydrogels as biomaterials lies in the similarity of their physical properties to those of natural tissue in its biological environment [4]. This resemblance is based on their water content, soft and rubbery consistency and low interfacial tension with water or biological fluids [5]. More- reserved